Not respecting your sleep and wake cycles could disrupt the functioning of our cells and thus contribute to the development of diseases.
Getting up early and going to bed late, not meeting your sleep needs or stringing together several sleepless nights is not only bad for our mood and our mental health. Our body also suffers from this disruption of the internal clock. Subjected to severe test, weakened, the latter would then be more predisposed to develop certain pathologies.
Here is the conclusion reached by researchers at the University of South Carolina (USC), in the United States. In their work, published in the journal Proceedings of the National Academy of Sciences, they explain that they have found a new timing mechanism within liver cells. These, essential for the proper functioning of some of our organs, can also contribute to the development of diseases such as diabetes or cancer when their natural rhythm is disturbed.
“Epidemiological studies are increasingly revealing links between modern lifestyles and our internal biological clock, and when these two factors clash, it can lead to the development of diseases like obesity and breast cancer,” says Steve Kay, director of convergent biosciences and senior professor of neurology, biomedical engineering, and biological sciences at the Michelson Center for Convergent Biosciences at USC. “This study goes beyond epidemiology to explore the mechanisms of circadian disruption as a risk factor for certain diseases.”
The key role of the HNF4A receptor
Circadian rhythms correspond to the behavioral patterns of living beings that follow a cycle of approximately 24 hours. Our sleep-wake cycle is one of the major circadian rhythms that responds to light and dark, day and night. Disrupting this cycle can lead to health problems in humans, so scientists are studying cell behavior to see how the interrupted clock can cause disease – an important step towards targeted medical treatments.
The lead being considered by the USC researchers is that of the nuclear receptor protein HNF4A, which is involved in the embryonic development of the liver, kidneys and intestine. By examining liver and colon cells from mice and humans, the scientific team discovered that the nuclear receptor HNF4A is intimately linked to the circadian clock of these organs and that it can repress the functioning of CLOCK genes. and BMAL1, which act as key molecular cogs determining circadian rhythms in mammals.
Mutations in HNF4A causing disease
Present in the cell nucleus, nuclear receptors receive chemical signals from the cell and associate with other proteins to release specific genes that regulate cell development, homeostasis and metabolism. Receptors act at the crossroads of cellular circuits by integrating the information necessary for the normal functioning of cells. According to the researchers, nuclear receptors are potential targets for drugs aimed at fighting diseases, including reproductive disorders, inflammation, cancer, diabetes, cardiovascular disease and obesity. They thus discovered for the first time that the circadian clock modulates the daily cycles of the classic functions of HNF4A as a nuclear receptor.
“Inside the cell, the clockwork is universal, but the clock hands are specific to each organ, so the way the clock works in each cell is different,” says Steve. Kay. “So in the liver, we looked at tissue-specific proteins and found that HNF4A is related to the circadian clock, it’s regulated by the clock. That’s the new finding and it’s a big step forward.”
Our rhythms of life contribute to making us sick
The role of the HNF4A receptor is therefore fundamental in the regulation of circadian cycles. Mutations in this gene are also “known to contribute to a rare hereditary form of diabetes called MODY1, and its dysregulation of expression has been closely linked to liver cancer, two mechanisms that we do not fully understand”, acknowledges Meng Qu , associate researcher at the Michelson Center. “Our finding suggests that clock disruption could be a potential mechanism and provide a bridge between circadian regulation and disease development.”
For Dr. Kay, this new work will make it possible to “understand how the disruption of our highly evolved circadian lifestyle makes us sick”. “Humans are not made for night shifts, night lights, and intercontinental travel. The challenges of modern life to our circadian system pose a long-term threat to our health,” he concludes.
.